tbuckley/cabot-search huggingface dataset:
Influenza and COVID-19 Vaccination Coverage Among Health Care Personnel — United States, 2021–22
Authors: Hilda Razzaghi, Anup Srivastav, Marie A. de Perio, A. Scott Laney, Carla L. Black
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The Advisory Committee on Immunization Practices (ACIP) and CDC recommend that all health care personnel (HCP) receive annual influenza vaccination to reduce influenza-related morbidity and mortality among these personnel and their patients (1). ACIP also recommends that all persons aged ≥6 months, including HCP, be vaccinated with COVID-19 vaccines and remain up to date (2,3). During March 29-April 19, 2022, CDC conducted an opt-in Internet panel survey of 3,618 U.S. HCP to estimate influenza vaccination coverage during the 2021-22 influenza season as well as receipt of the primary COVID-19 vaccination series and a booster dose. Influenza vaccination coverage was 79.9% during the 2021-22 season, and 87.3% of HCP reported having completed the primary COVID-19 vaccination series; among these HCP, 67.1% reported receiving a COVID-19 booster dose. Among HCP, influenza, COVID-19 primary series, and COVID-19 booster dose vaccination coverage were lowest among assistants and aides, those working in long-term care (LTC) or home health care settings, and those whose employer neither required nor recommended the vaccines. Overall, employer requirements for influenza and COVID-19 primary series vaccines were reported by 43.9% and 59.9% of HCP, respectively; among HCP who completed the primary series of COVID-19 vaccines, 23.5% reported employer requirements for COVID-19 booster vaccines. Vaccination coverage for all three vaccine measures was higher among HCP who reported employer vaccination requirements and ranged from 95.8% to 97.3% for influenza, 90.2% to 95.1% for COVID-19 primary series, and 76.4% to 87.8% for COVID-19 booster vaccinations among HCP who completed the primary series of COVID-19 vaccines, by work setting. Implementing workplace strategies demonstrated to improve vaccination coverage among HCP, including vaccination requirements or active promotion of vaccination, can increase influenza and COVID-19 vaccination coverage among HCP and reduce influenza and COVID-19-related morbidity and mortality among HCP and their patients (4).
Cystic fibrosis macrophage function and clinical outcomes after elexacaftor/tezacaftor/ivacaftor
Authors: Shuzhong Zhang, Chandra L. Shrestha, Frank Robledo-Avila, Devi Jaganathan, Benjamin L. Wisniewski, Nevian Brown, Hanh Pham, Katherine Carey, Amal O. Amer, Luanne Hall-Stoodley, Karen S. McCoy, Shasha Bai, Santiago Partida-Sanchez, Benjamin T. Kopp
Journal: European Respiratory Journal (2022)

Background Abnormal macrophage function caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) is a critical contributor to chronic airway infections and inflammation in people with cystic fibrosis (PWCF). Elexacaftor/tezacaftor/ivacaftor (ETI) is a new CFTR modulator therapy for PWCF. Host–pathogen and clinical responses to CFTR modulators are poorly described. We sought to determine how ETI impacts macrophage CFTR function, resulting effector functions and relationships to clinical outcome changes. Methods Clinical information and/or biospecimens were obtained at ETI initiation and 3, 6, 9 and 12 months post-ETI in 56 PWCF and compared with non-CF controls. Peripheral blood monocyte-derived macrophages (MDMs) were isolated and functional assays performed. Results ETI treatment was associated with increased CF MDM CFTR expression, function and localisation to the plasma membrane. CF MDM phagocytosis, intracellular killing of CF pathogens and efferocytosis of apoptotic neutrophils were partially restored by ETI, but inflammatory cytokine production remained unchanged. Clinical outcomes including increased forced expiratory volume in 1 s (+10%) and body mass index (+1.0 kg·m −2 ) showed fluctuations over time and were highly individualised. Significant correlations between post-ETI MDM CFTR function and sweat chloride levels were observed. However, MDM CFTR function correlated with clinical outcomes better than sweat chloride. Conclusion ETI is associated with unique changes in innate immune function and clinical outcomes.
Progress Toward Poliomyelitis Eradication — Pakistan, January 2021–July 2022
Authors: Chukwuma Mbaeyi, Shahzad Baig, Muhammad Rana Safdar, Zainul Khan, Hamish Young, Jaume Jorba, Zubair M. Wadood, Hamid Jafari, Muhammad Masroor Alam, Richard Franka
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

After reporting a single wild poliovirus (WPV) type 1 (WPV1) case in 2021, Pakistan reported 14 cases during April 1-July 31, 2022. Pakistan and Afghanistan are the only countries where endemic WPV transmission has never been interrupted (1). In its current 5-year strategic plan, the Global Polio Eradication Initiative (GPEI) has set a goal of interrupting all WPV1 transmission by the end of 2023 (1-3). The reemergence of WPV cases in Pakistan after 14 months with no case detection has uncovered transmission in southern Khyber Pakhtunkhwa province, the most historically challenging area. This report describes Pakistan's progress toward polio eradication during January 2021-July 2022 and updates previous reports (4,5). As of August 20, 2022, all but one of the 14 WPV1 cases in Pakistan during 2022 have been reported from North Waziristan district in Khyber Pakhtunkhwa. In underimmunized populations, excretion of vaccine virus can, during a period of 12-18 months, lead to reversion to neurovirulence, resulting in circulating vaccine-derived polioviruses (cVDPVs), which can cause paralysis and outbreaks. An outbreak of cVDPV type 2 (cVDPV2), which began in Pakistan in 2019, has been successfully contained; the last case occurred in April 2021 (1,6). Despite program improvements, 400,000-500,000 children continue to be missed during nationwide polio supplementary immunization activities (SIAs),* and recent isolation of poliovirus from sewage samples collected in other provinces suggests wider WPV1 circulation during the ongoing high transmission season. Although vaccination efforts have been recently complicated by months of flooding during the summer of 2022, to successfully interrupt WPV1 transmission in the core reservoirs in southern Khyber Pakhtunkhwa and reach the GPEI goal, emphasis should be placed on further improving microplanning and supervision of SIAs and on systematic tracking and vaccination of persistently missed children in these reservoir areas of Pakistan.
Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial
Authors: Victoria Hodgetts Morton, Philip Toozs-Hobson, Catherine A Moakes, Lee Middleton, Jane Daniels, Nigel A B Simpson, Andrew Shennan, Fidan Israfil-Bayli, Andrew K Ewer, Jim Gray, Mark Slack, Jane E Norman, Christoph Lees, Konstantinos Tryposkiadis, Max Hughes, Peter Brocklehurst, R Katie Morris
Journal: The Lancet (2022)

BackgroundMiscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage.MethodsC-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349.FindingsBetween Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI –0·02 to 0·03]).InterpretationMonofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes.FundingNational Institute of Health Research Health Technology Assessment Programme.
Muscarinic acetylcholine receptors for psychotic disorders: bench-side to clinic
Authors: Samantha E. Yohn, Peter J. Weiden, Christian C. Felder, Stephen M. Stahl
Journal: Trends in Pharmacological Sciences (2022)

Modern interest in muscarinic acetylcholine receptor (mAChR) activators for schizophrenia began in the 1990s when xanomeline, an M1/M4-preferring mAChR agonist developed for cognitive symptoms of Alzheimer's disease (AD), had unexpected antipsychotic activity. However, strategies to address tolerability concerns associated with activation of peripheral mAChRs were not available at that time. The discovery of specific targeted ligands and combination treatments to reduce peripheral mAChR engagement have advanced the potential of mAChR activators as effective treatments for psychotic disorders. This review provides perspectives on the background of the identification of mAChRs as potential antipsychotics, advances in the preclinical understanding of mAChRs as targets, and the current state of mAChR activators under active clinical development for schizophrenia.
Reply to Fabio Campodonico, Francesca Mattioli, and Carlo Introini’s Letter to the Editor re: Wei Shen Tan, Aaron Pendergast, Charlotte Ackerman, et al. Intravesical Chemohyperthermia Versus Passive Chemotherapy in Patients with Intermediate-risk Non–muscle-invasive Bladder Cancer (HIVEC-II): A Phase 2, Open-label, Randomised Controlled Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.08.003
Authors: Wei Shen Tan, John D. Kelly
Journal: European Urology (2022)
Prescribing and adjusting exercise training in chronic respiratory diseases – Expert-based practical recommendations
Authors: R. Gloeckl, R.H. Zwick, U. Fürlinger, I. Jarosch, T. Schneeberger, D. Leitl, A.R. Koczulla, K. Vonbank, C. Alexiou, I. Vogiatzis, M.A. Spruit
Journal: Pulmonology (2022)

International guidelines recommend endurance (ET) and strength training (ST) in patients with chronic respiratory diseases (CRDs), but only provide rough guidance on how to set the initial training load. This may unintentionally lead to practice variation and inadequate training load adjustments. This study aimed to develop practical recommendations on tailoring ET and ST based on practices from international experts from the field of exercise training in CRDs.35 experts were invited to address a 64-item online survey about how they prescribe and adjust exercise training.Cycling (97%) and walking (86%) were the most commonly implemented ET modalities. Continuous endurance training (CET, 83%) and interval endurance training (IET, 86%) were the frequently applied ET types. Criteria to prescribe IET instead of CET were: patients do not tolerate CET due to dyspnoea at the initial training session (79%), intense breathlessness during initial exercise assessment (76%), and/or profound exercise-induced oxygen desaturation (59%). For ST, most experts (68%) recommend 3 sets per exercise; 62% of experts set the intensity at a specific load that patients can tolerate for a range of 8 to 15 repetitions per set. Also, 56% of experts advise patients to approach local muscular exhaustion at the end of a single ST set.The experts´ practices were summarized to develop practical recommendations in the form of flowcharts on how experts apply and adjust CET, IET, and ST in patients with CRDs. These recommendations may guide health care professionals to optimize exercise training programs in patients with CRDs.
Breakthrough of extracellular vesicles in pathogenesis, diagnosis and treatment of osteoarthritis
Authors: Zichang Liu, Yu Zhuang, Lianfei Fang, Changyong Yuan, Xudong Wang, Kaili Lin
Journal: Bioactive Materials (2022)

Osteoarthritis (OA) is a highly prevalent whole-joint disease that causes disability and pain and affects a patient's quality of life. However, currently, there is a lack of effective early diagnosis and treatment. Although stem cells can promote cartilage repair and treat OA, problems such as immune rejection and tumorigenicity persist. Extracellular vesicles (EVs) can transmit genetic information from donor cells and mediate intercellular communication, which is considered a functional paracrine factor of stem cells. Increasing evidences suggest that EVs may play an essential and complex role in the pathogenesis, diagnosis, and treatment of OA. Here, we introduced the role of EVs in OA progression by influencing inflammation, metabolism, and aging. Next, we discussed EVs from the blood, synovial fluid, and joint-related cells for diagnosis. Moreover, we outlined the potential of modified and unmodified EVs and their combination with biomaterials for OA therapy. Finally, we discuss the deficiencies and put forward the prospects and challenges related to the application of EVs in the field of OA.
Inclusion of a core patient-reported outcomes battery in adolescent and young adult cancer clinical trials
Authors: Michael E Roth, Susan K Parsons, Patricia A Ganz, Lynne I Wagner, Pamela S Hinds, Sarah Alexander, Kristin Bingen, Sharon L Bober, Julienne Brackett, David Cella, N Lynn Henry, Daniel J Indelicato, Rebecca H Johnson, Tamara P Miller, Shoshana M Rosenberg, Kathryn H Schmitz, Gita Thanarajasingam, Bryce B Reeve, John M Salsman
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Disparities in care, treatment-related toxicity and health-related quality of life (HRQoL) for adolescents and young adults (AYAs, aged 15-39 years) with cancer are under-addressed partly because of limited collection of patient-reported outcomes (PROs) in cancer clinical trials (CCTs). The AYA years include key developmental milestones distinct from younger and older patients, and cancer interrupts attainment of critical life goals. Lack of consensus on a standardized approach to assess HRQoL and treatment-related toxicity in AYA CCTs has limited the ability to improve patient outcomes. The National Cancer Institute’s Clinical Trials Network AYA PRO Task Force was assembled to reach consensus on a core set of PROs and foster its integration into AYA CCTs. Eight key considerations for selecting the core PRO AYA battery components were identified: relevance to AYAs; importance of constructs across the age continuum; prioritization of validated measures; availability of measures without licensing fees; availability in multiple languages; applicability to different cancer types and treatments; ability to measure different HRQoL domains and toxicities; and minimized burden on patients and sites. The Task Force used a modified Delphi approach to identify key components of the PRO battery. The Patient-Reported Outcomes Measurement Information System (PROMIS) and the PRO Common Terminology Criteria for Adverse Events Measurement System met all criteria and were selected to assess HRQoL and treatment toxicity, respectively. Investigators are rapidly incorporating the recommendations of the Task Force into AYA trials. Inclusion of a standardized assessment of HRQoL and treatment toxicities in AYA CCTs is a vital first step to develop interventions to improve health outcomes for AYAs diagnosed with cancer.
NanoSPECT imaging reveals the uptake of 123I-labelled oxidized low-density lipoprotein in the brown adipose tissue of mice via CD36
Authors: Kento Hosomi, Hidekazu Kawashima, Atsushi Nakano, Akemi Kakino, Yuko Okamatsu-Ogura, Yuki Yamashita, Mai Sasaoka, Daisaku Masuda, Shizuya Yamashita, Chu-Huang Chen, Shunsuke Yuzuriha, Hiroshi Hosoda, Hidehiro Iida, Tatsuya Sawamura
Journal: Cardiovascular Research (2022)

Abstract Aims The liver is the major organ shown to remove oxidized low-density lipoprotein (oxLDL) from the circulation. Given increased evidence that thermogenic adipose tissue has anti-effects, we used 123I-labelled oxLDL as a tracer to reveal oxLDL accumulation in the brown adipose tissue (BAT) of mice. We also explored the mechanisms of oxLDL accumulation in BAT. Methods and results We used high-resolution nanoSPECT/CT to investigate the tissue distribution of 123I-oxLDL and 123I-LDL (control) following intravenous injection into conscious mice. 123I-oxLDL distribution was discovered in BAT at an intensity equivalent to that in the liver, whereas 123I-LDL was detected mostly in the liver. Consistent with the function of BAT related to sympathetic nerve activity, administering anaesthesia in mice almost completely eliminated the accumulation of 123I-oxLDL in BAT, and this effect was reversed by administering β3-agonist. Furthermore, exposing mice to cold stress at 4°C enhanced 123I-oxLDL accumulation in BAT. Because in 123I-oxLDL, the protein of oxLDL was labelled, we performed additional experiments with DiI-oxLDL in which the lipid phase of oxLDL was fluorescently labelled and observed similar results, suggesting that the whole oxLDL particle was taken up by BAT. To identify the receptor responsible for oxLDL uptake in BAT, we analysed the expression of known oxLDL receptors (e.g. SR-A, CD36, and LOX-1) in cultured brown adipocyte cell line and primary brown adipocytes and found that CD36 was the major receptor expressed. Treatment of cells with CD36 siRNA or CD36 neutralizing antibody significantly inhibited DiI-oxLDL uptake. Finally, CD36 deletion in mice abolished the accumulation of 123I-oxLDL and DiI-oxLDL in BAT, indicating that CD36 is the major receptor for oxLDL in BAT. Conclusion We show novel evidence for the CD36-mediated accumulation of oxLDL in BAT, suggesting that BAT may exert its anti-atherogenic effects by removing atherogenic LDL from the circulation.
Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities
Authors: Tongxin Ge, Xiang Gu, Renbing Jia, Shengfang Ge, Peiwei Chai, Ai Zhuang, Xianqun Fan
Journal: Cancer Communications (2022)

Reversible, spatial, and temporal regulation of metabolic reprogramming and epigenetic homeostasis are prominent hallmarks of carcinogenesis. Cancer cells reprogram their metabolism to meet the high bioenergetic and biosynthetic demands for vigorous proliferation. Epigenetic dysregulation is a common feature of human cancers, which contributes to tumorigenesis and maintenance of the malignant phenotypes by regulating gene expression. The epigenome is sensitive to metabolic changes. Metabolism produces various metabolites that are substrates, cofactors, or inhibitors of epigenetic enzymes. Alterations in metabolic pathways and fluctuations in intermediate metabolites convey information regarding the intracellular metabolic status into the nucleus by modulating the activity of epigenetic enzymes and thus remodeling the epigenetic landscape, inducing transcriptional responses to heterogeneous metabolic requirements. Cancer metabolism is regulated by epigenetic machinery at both transcriptional and post-transcriptional levels. Epigenetic modifiers, chromatin remodelers and non-coding RNAs are integral contributors to the regulatory networks involved in cancer metabolism, facilitating malignant transformation. However, the significance of the close connection between metabolism and epigenetics in the context of cancer has not been fully deciphered. Thus, it will be constructive to summarize and update the emerging new evidence supporting this bidirectional crosstalk and deeply assess how the crosstalk between metabolic reprogramming and epigenetic abnormalities could be exploited to optimize treatment paradigms and establish new therapeutic options. In this review, we summarize the central mechanisms by which epigenetics and metabolism reciprocally modulate each other in cancer and elaborate upon and update the major contributions of the interplays between epigenetic aberrations and metabolic rewiring to cancer initiation and development. Finally, we highlight the potential therapeutic opportunities for hematological malignancies and solid tumors by targeting this epigenetic-metabolic circuit. In summary, we endeavored to depict the current understanding of the coordination between these fundamental abnormalities more comprehensively and provide new perspectives for utilizing metabolic and epigenetic targets for cancer treatment.
Venetoclax and idasanutlin in relapsed/refractory AML: a nonrandomized, open-label phase 1b trial
Authors: Naval G. Daver, Monique Dail, Jacqueline S. Garcia, Brian A. Jonas, Karen W. L. Yee, Kevin R. Kelly, Norbert Vey, Sarit Assouline, Gail J. Roboz, Stefania Paolini, Daniel A. Pollyea, Agostino Tafuri, Joseph M. Brandwein, Arnaud Pigneux, Bayard L. Powell, Pierre Fenaux, Rebecca L. Olin, Giuseppe Visani, Giovanni Martinelli, Maika Onishi, Jue Wang, Weize Huang, Cherie Green, Marion G. Ott, Wan-Jen Hong, Marina Y. Konopleva, Michael Andreeff
Journal: Blood (2022)

This phase 1b trial (NCT02670044) evaluated venetoclax-idasanutlin in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) ineligible for cytotoxic chemotherapy. Two-dimensional dose escalation (DE, n = 50) was performed for venetoclax daily with idasanutlin on days 1 to 5 in 28-day cycles, followed by dosing schedule optimization (n = 6) to evaluate reduced venetoclax schedules (21-/14-day dosing). Common adverse events (occurring in ≥40% of patients) included diarrhea (87.3% of patients), nausea (74.5%), vomiting (52.7%), hypokalemia (50.9%), and febrile neutropenia (45.5%). During DE, across all doses, composite complete remission (CRc; CR + CR with incomplete blood count recovery + CR with incomplete platelet count recovery) rate was 26.0% and morphologic leukemia-free state (MLFS) rate was 12%. For anticipated recommended phase 2 doses (venetoclax 600 mg + idasanutlin 150 mg; venetoclax 600 mg + idasanutlin 200 mg), the combined CRc rate was 34.3% and the MLFS rate was 14.3%. Pretreatment IDH1/2 and RUNX1 mutations were associated with higher CRc rates (50.0% and 45.0%, respectively). CRc rate in patients with TP53 mutations was 20.0%, with responses noted among those with co-occurring IDH and RUNX1 mutations. In 12 out of 36 evaluable patients, 25 emergent TP53 mutations were observed; 22 were present at baseline with low TP53 variant allele frequency (median 0.0095% [range, 0.0006-0.4]). Venetoclax-idasanutlin showed manageable safety and encouraging efficacy in unfit patients with R/R AML. IDH1/2 and RUNX1 mutations were associated with venetoclax-idasanutlin sensitivity, even in some patients with co-occurring TP53 mutations; most emergent TP53 clones were preexisting. Our findings will aid ongoing/future trials of BCL-2/MDM2 inhibitor combinations. This trial was registered at www.clinicaltrials.gov as #NCT02670044.